Supernatant fluids of mitogen-activated human tonsil lymphocytes contain factors which are toxic to indicator tumor cells (mouse L-929 cells) and other factors which are not toxic but inhibit DNA synthesis. The former are called lymphotoxins (LT); the latter, inhibitors of DNA synthesis (IDS). After extensive purification to apparent homogeneity, alpha-LT is found to be 79,000 daltons in size, but separable into approximately 50,000 and 25,000 daltons subunits. Preliminary work suggests that the 50,000 polypeptide is the biologically active unit. Cell-free extracts contain only a 45,000 dalton, biologically active LT. This compares with supernatant LT's from mouse, rat and guinea pig, all of which are in the 45 - 55,000 dalton class. The 79,000 alpha-LT contains RNase activity of a unique kind; it digests both single stranded RNA and the RNA strand of an RNA-DNA hybrid. Polyacrylamide gel electrophoresis in 8 M urea gives equivocal results in that RNase activity disappears, but is not recovered in other fractions. This may be due to an artefact in assaying for RNase in urea-containing samples. IDS has been purified less extensively than alpha-LT but to a point clearly removing any alpha-LT contaminants. It has the property of inhibiting DNA polymerase alpha in vitro and appears to have characteristics of the recently described DNA-binding proteins. BIBLIOGRAPHIC REFERENCES: Walker, S.M., Lee, S.-C. and Lucas, Z.J. Cytotoxic activity of lymphocytes. VI. Heterogeneity of cytotoxins in supernatants of mitogen-activated lymphocytes. J. Immunol. 116:807, 1976. Lee, S.-C. and Lucas, Z.J. Regulatory factors produced by lymphocytes. I. The occurrence of multiple alpha-lymphotoxins associated with ribonuclease activity. J. Immunol. 117:283, 1976.